Unravelling the origins of life with mathematical chemistry

How life began is one of the most compelling questions humanity
has ever asked. Atoms and molecules, driven by nothing more than
unthinking chemical processes, somehow became the complex
reproductive organisms that we see roaming the Earth today --
somehow, they became us.

Those tiny baby steps at the start of life, when some unknown
molecule somehow became self-replicating, for example, hold the key
to understanding how life began and how likely it is to have
sprouted throughout the Universe.

Martin Hanczyc, from the University of Southern Denmark, has
dedicated his professional life to this area of study. His popular
TED Talk from 2011 is a great discussion of the blurred line
between life and non-life.

Now, using a new computational approach to mapping how simple
molecules like hydrogen cyanide become more complex, he's hoping to
find those first chemicals that bridged the divide and became
living.

"Hydrogen cyanide is a very simple molecule with only three
atoms […] but it can combine with other things to make more
complicated molecules," he explains. "Some of those molecules have
a complexity like the molecules found in biology, so if you need a
starting material to build the biochemistry of a cell, that's a
good place to start."

Hanczyc holds a sample of reacted hydrogen cyanide

Birgitte Svennevig/SDU

In particular, hydrogen cyanide has been previously shown to
play a part in the creation of adenine, one of the building blocks
of DNA and RNA. An adenine-creation pathway was first
demonstrated in the 60s, but the probability that hydrogen
cyanide will naturally lead to a biologically important molecule is
not well-known.

"We don't know the whole reaction landscape," says Hanczyc.
"Understanding the larger landscape […] gives us a more intuitive
sense about how likely it is that hydrogen cyanide can give rise to
something biologically relevant."

That knowledge is important because hydrogen cyanide is found
across the Universe. If there are hundreds of different ways for
hydrogen cyanide to help produce adenine, then maybe this building
block for life is being created on those far off exoplanets discovered by Kepler.

To help discover those possible pathways, Hanczyc turned to
mathematics. For the past two years he has been working with Daniel
Merkle, of the Department of Mathematics and Computer Science at
the University of Southern Denmark.

Using mathematical models, Merkle is able to map the trillions
of different possible molecules and pathways that can arise when
hydrogen cyanide is left to react. By comparing that map with
experimental results from Hanczyc's lab, Merkle can narrow down the
field and then begin to identify interesting patterns in the
data.

"When hydrogen cyanide reacts [there are] a trillion possible
different molecules," says Merkle. "[…] We ask [the question] is
there a structural [mathematical] property that's interesting from
a chemistry point of view."

For example, if one of the molecules generated by the model has
a mathematical property similar to self-replication, this might be
a candidate for further experimentation in the lab. The approach,
detailed by Hanczyc in a keynote speech at the European Conference on
Artificial Life in Taormina, Italy on 5 September, helps target
the research towards potential pre-cursors to life.

"Life started from a chaotic state, so how to organise things?
Having chemical reactions that reinforce themselves is one way of
doing this. But these types of reactions in reality are very
difficult to find," says Hancyzc. "We need new tools to understand
the complexity of the [chemical] systems that we need to make in
order to answer these scientific questions."

So-called "generative chemistry", where mathematicians provide a
menu for experimentalists to focus their efforts on could well be
one of the new tools that help us better understand the origins of
life.

And if Hancyzc and Merkle find a hydrogen cyanide reaction
product that self-replicates, it might suggest that somewhere in
the masses of hydrogen cyanide across the Universe, a little
self-replicating chemical is taking the first steps towards
life.